Herpes simplex virus type 2 (HHV-2) is one of the most common sexually transmitted diseases in the world. In the immunocompromised host, including patients with human immunodeficiency virus (HIV), herpes simplex virus is at high risk for reactivation. We present a woman with HIV and a large ulcer of the palm determined to be HHV-2. Not only was the location of her ulcer unusual, but her CD4 lymphocyte count continued to drop despite improvement of the palmar ulceration with treatment. As a result, her palmar HHV-2 ulcer became an AIDS-defining complex.